Author + information
- George S. Stergiou, MD, PhDa,∗ (, )
- Anastasios Kollias, MD, PhDa and
- Athanase D. Protogerou, MD, PhDb
- aHypertension Center STRIDE-7, National and Kapodistrian University of Athens, School of Medicine, Third Department of Medicine, Sotiria Hospital, Athens, Greece
- bDepartment of Pathophysiology, Cardiovascular Prevention & Research Unit, National and Kapodistrian University of Athens, School of Medicine, Laiko Hospital, Athens, Greece
- ↵∗Address for correspondence:
Dr. George S. Stergiou, Hypertension Center, STRIDE-7, Third University Department of Medicine, Sotiria Hospital, 152 Mesogion Avenue, Athens 11527, Greece.
The measurement of blood pressure (BP) aims to quantify the mechanical stress that BP exerts on the arterial tree, namely, the perpendicular force over the unit of area applied from the blood to the inner surface of the arterial wall. Despite major developments in the management of hypertension in the last half century, important issues related to BP measurement methodology remain astonishingly untackled and/or difficult to address (1), which are largely attributed to 2 interrelated but quite discrete facts.
First, there is a “measurement error” of the conventional BP measurement method, namely, the inaccuracy of the noninvasive “estimation” of the pressure in the brachial artery using the auscultatory arm-cuff method. In comparison to the true intra-arterial brachial BP, the inaccuracy of the arm-cuff method has been repeatedly documented (2). Second, the other fact is the well-known inherent physiological BP variability, which is subject-, time-, and arterial site−dependent (1,2).
In this issue of the Journal, Picone et al. (3) provided revealing evidence on both the measurement error and the arterial site−dependent variability by performing meta-analyses of studies that compared: 1) intra-arterial brachial BP versus cuff-brachial BP; 2) intra-arterial brachial BP versus intra-aortic BP; and 3) cuff-brachial BP versus intra-aortic BP (3). These analyses provide convincing proof on: 1) the inaccuracy of the cuff-brachial BP measurement technologies (auscultatory and oscillometric); 2) the magnitude of the so-called pulse pressure (PP) amplification (aortic versus brachial BP difference); and 3) the unexpected similarity of cuff-brachial BP with intra-aortic systolic BP.
These results should be considered by taking into account some important limitations (3). First, invasive BP measurements were performed in selected populations and might not equally apply to other age groups or disease states. Second, there was a potential selection bias because 50% of the studies identified could not be included. Third, there was considerable heterogeneity among studies regarding the BP measurement protocol, and several studies with too small a sample size were included. However, it is fair to say that Picone et al. (3) presented to the scientific community the most serious attempt to review the published evidence on cuff-brachial BP versus intra-arterial BP versus aortic BP measurements. It is surprising that such serious analyses of the evidence on crucial BP measurement methodology issues have not become available for such a long time.
For the first time, this meta-analysis carefully quantified the measurement error of the cuff-brachial methods to assess intra-arterial brachial BP (3). The results showed considerable underestimation of systolic BP (6 mm Hg) and overestimation of diastolic BP (6 mm Hg), which led to a large underestimation of PP (12 mm Hg). The oscillometric method showed similar behavior with the auscultatory method, which is well expected because the former was developed to simulate the latter. These findings question the accuracy of the BP-associated cardiovascular risk stratification, with substantial clinical implications. Nevertheless, for half a century, the noninvasive cuff-brachial BP assessment provided valid biomarkers (systolic BP, diastolic BP, and PP), which have been successfully used to stratify and massively prevent cardiovascular disease in clinical practice. In contrast, the evidence on the prognostic value of invasive brachial BP is limited (4), and there are no studies comparing it against arm-cuff measurements.
Because the cuff-brachial BP assessment seems to incorporate a systematic error compared with intra-arterial BP, it might be argued that there might be no substantial difference on the BP-associated cardiovascular risk relationship curve. Novel noninvasive reference technologies that will provide accurate estimation of the true intra-arterial brachial BP need to be developed to allow valid comparisons against the conventional arm-cuff BP measurement in outcome clinical trials.
The physiological age-dependent phenomenon of systolic BP amplification across the arterial tree was confirmed by Picone et al. using invasive measurements (3). For selected subjects included in this analysis (age 54 to 64 years; men 72%), the intra-arterial systolic BP amplification was 8 mm Hg. These invasive findings were almost identical to the noninvasive calculation of the systolic BP amplification (50th percentile 8 and 9 mm Hg for men with or without cardiovascular risk factors, respectively, age 50 to 59 years) (5). Thus, despite the errors in the noninvasive central BP calculation, the systolic BP amplification estimation appears to give similar values as the intra-arterial measurement, at least in middle-aged men.
The third meta-analysis by Picone et al. (3) that evaluated the cuff-brachial BP versus the intra-aortic BP difference gave expected but also puzzling findings. These results confirmed recent findings by Sharman et al. (2) that showed the average cuff-brachial systolic BP to be comparable with the intra-aortic systolic BP, which is in line with cuff-brachial systolic BP underestimation versus the intra-arterial brachial BP measurement. This underestimation appears to negate the amplification phenomenon between the aorta and the brachial artery. However, the absolute differences between cuff-brachial and intra-aortic systolic BP were large and bi-directional (i.e., associated with either overestimation or underestimation of the intra-aortic systolic BP), which indicated random errors rather than systematic errors (mean difference 0.3 mm Hg; absolute difference 8 mm Hg).
The preceding findings have direct implications on the research conducted in the past 20 years that has investigated the potential clinical superiority of aortic (central) over brachial BP in cardiovascular risk prediction. Recent meta-analyses of noninvasive and invasive studies showed marginal superiority of central BP versus brachial BP in determining target organ damage and cardiovascular outcomes (6,7). However, to test the hypothesis of the aortic BP superiority, BP measurement methodologies need to be used at both arterial sites that will correctly assess the amplification phenomenon. This fact has been overlooked in several studies for several reasons. First, noninvasive, easy to use, central BP monitors have recently become available in clinical practice, yet their accuracy in the estimation of pressure amplification depends on the accuracy of methods used to calibrate the peripheral artery waveform (1,2). Second, as shown in the analysis by Picone et al. (3), the amplification phenomenon (at least regarding the systolic BP but not the PP) may be minimized when comparing invasive aortic data versus the cuff-brachial derived measurement. Thus, the data in favor of central over brachial BP may be affected by several methodological issues. Third, it has been shown that the pressure amplification exhibits time-dependent variability and a sleep-dipping pattern, which cannot be appreciated in static conditions (8). In other words, the interaction of the time-dependent and arterial site−dependent elements of BP variability must be taken into consideration to correctly test the hypothesis of the clinical superiority of the aortic BP versus the brachial BP, which is only feasible using simultaneous 24-h ambulatory aortic and brachial BP monitoring.
From the scientific and the physiological point of view, the invasive intra-arterial BP measurements are the meaningful and relevant ones. In contrast, the science of clinical medicine and hypertension (BP as a vital sign or a marker for hypertension disease, respectively) applied for half a century in billions of people around the world has been inevitably based on noninvasive arm-cuff BP measurements. Despite the remaining important methodological issues in arterial BP measurement, which were nicely demonstrated in the analyses by Picone et al. (3), hypertension management in clinical practice has been a great success story in medicine. Whether the more accurate measurement of brachial BP or the implementation of accurate aortic (central) BP measurement in clinical practice can contribute to more efficient prevention of cardiovascular disease are challenging research questions. To allow these questions to be addressed, novel noninvasive technologies that provide such measurements in static and dynamic conditions need to be developed and properly validated. These are the 21st century questions on BP measurement methodology that the scientific community should put on its research agenda.
↵∗ Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- 2017 American College of Cardiology Foundation
- Stergiou G.S.,
- Parati G.,
- Vlachopoulos C.,
- et al.
- Sharman J.E.,
- Avolio A.P.,
- Baulmann J.,
- et al.
- Picone D.S.,
- Schultz M.G.,
- Otahal P.,
- et al.
- Fagard R.H.,
- Pardaens K.,
- Staessen J.A.,
- Thijs L.
- Herbert A.,
- Cruickshank J.K.,
- Laurent S.,
- Boutouyrie P.,
- Reference Values for Arterial Measurements Collaboration
- Kollias A.,
- Lagou S.,
- Zeniodi M.E.,
- Boubouchairopoulou N.,
- Stergiou G.S.
- Vlachopoulos C.,
- Aznaouridis K.,
- O'Rourke M.F.,
- Safar M.E.,
- Baou K.,
- Stefanadis C.